Acute graft versus host disease after liver transplantation: patterns of lymphocyte chimerism

The diagnosis of acute graft versus host disease (aGVHD) following liver transplantation can be difficult, since many of the clinical signs can be caused by drug reactions or viral infections. To establish criteria for the persistence of donor T-cells versus engraftment, we measured donor T-cells by short tandem repeat (STR) assays in 49 liver transplant patients for 8 or more weeks post-transplant. Donor CD3+ T-cells were detected in 38 of 49 patients, on POD 2 with a mean level of 5%. The top of the 99% confidence interval for weeks 1, 2, 3, 4 and 8 were 11, 6, 3, 2 and 3%. Donor CD8+ T-cells were measured in eight patients. The level of CD8+ T-cells was much less than that for CD3+ T-cells, except in two cases of apparent aGVHD. One patient developed severe aGVHD with donor T-cells as high as 84%. The other had 10% donor T-cells for more than 16 weeks associated with fever and neutropenia. We tested the sensitivity of PCR-ssp typing of HLA DR/DQ for donor T-cells. At least one donor type was detected in all samples with 1% or more donor DNA. Thus, higher levels of donor T-cell chimerism, particularly with a high proportion of CD8+ T-cells, strongly supports a diagnosis of aGVHD.